The objectives of this research proposal will be: a) identification of products of N-(4-(5-nitro-2-furyl)-2-thiazolyl)formamide (FANFT) and 2-amino-4-(5-nitro-2-furyl)-thiazole (ANFT) cooxidative metabolism; b) investigation of the mechanism of FANFT and ANFT cooxidative metabolism by prostaglandin endoperoxide synthetase (PES); c) determination of reactive intermediates formed during FANFT and ANFT cooxidative metabolism; d) determination of the distribution of renal FANFT deformylase activity; and e) determination of the in vivo effects of PES-mediated cooxidation on the incidence of chemically-induced urinary bladder cancer using feeding studies. Cooxidative metabolism will be defined as metabolism which is initiated by specific substrates and blocked by specific inhibitors of PES. Renal inner medullary microsomes and slices will be used to characterize cooxidative metabolism. Metabolites will be purified by gas liquid and high pressure liquid chromatographic techniques and identified by gas chromatograph mass spectral analysis. Metabolic requirements will be used to determine whether the fatty cyclooxygenase or prostaglandin hydroperoxidase activities of PES are involved in cooxidation. Radiolabeled FANFT and ANFT will be synthesized. The effect of aspirin or indomethacin, specific inhibitors of cooxidative metabolism, on the incidence of FANFT-induced bladder cancer will be examined. Urinary cooxidative metabolites of FANFT and ANFT will be identified. Urinary prostaglandin E2 will be analyzed by a specific radioimmunoassay technique. This proposal will provide further insight into the genesis of chemically-induced urinary bladder cancer and a more rational approach to its prevention.